Study explores link between assisted reproduction and prostate cancer risk

In a new national register study from Lund University in Sweden, researchers have studied the link between prostate cancer and infertility. The study, published in the British Medical Journal, includes over one million Swedish men.

Men who seek health care for infertility and assisted reproduction were shown to be at higher risk for prostate cancer than those who had become fathers by natural means."

Yvonne Lundberg Giwercman, professor of experimental pathology with a specialization in cancer at Lund University

Infertility and prostate cancer are conditions that each affect approximately one in every ten men. Previous research studying the link between infertility and prostate cancer have shown contradictory results. In this new study, researchers wanted to compare the risk of developing prostate cancer in three groups: those who become parents through IVF- and ICSI-assisted reproduction and those who had children through natural conception.

"Previous studies have often had small cohorts, short follow-up times and some have been based on self-reported diagnoses. In studies that have used sperm parameters as markers, for example sperm count and mobility, for the man's infertility, there is uncertainty as these can vary in the same man if measured at different times and can even differ from laboratory to laboratory", Yvonne Lundberg Giwercman explains.

The study was led by Yvonne Lundberg Giwercman and Yahia Al-Jebari, PhD student in reproductive medicine at Lund University. It is based on data collected from the Swedish Medical Birth Register of the 2.1 million children who were born between the years 1994 and 2014, which the researchers then matched with data from the National Quality Registry for Assisted Reproductive Technology and the Swedish Multi-Generation Register. They also studied and linked all the data with information from the Swedish Cancer Registry, Education Register and Cause of Death Register. Reporting of all fertility treatments in Swedish healthcare, both private and public, to the Quality Registry for Assisted Reproductive Technology is compulsory and therefore essentially comprehensive.

To avoid including fathers more than once, researchers excluded children in the birth register who were not first borns. Following this elimination, there were a total of 1181490 fathers and the same number of children. Of these fathers, 20618 had children with the assistance of in vitro fertilisation (IVF), 14882 with intracytoplasmic sperm injection (ICSI) and 1145990 via natural reproduction.

"When we compared these three patient groups we noticed that fathers who received IVF and ICSI treatment had 30 and 60 per cent higher risk of developing prostate cancer respectively, in comparison to fathers who had children without assisted reproduction. Of the men who developed prostate cancer there were 76 who were treated with IVF, 54 with ICSI and 3216 who had children via natural reproduction", says Yahia Al-Jebari, first author of the study.

The men who received infertility treatments also had a higher risk (IVF 1.33 and ICSI 1.64 times higher risk) of developing prostate cancer at a relatively young age (younger than 55 years), than those without assisted reproduction.

The study did not include data on the men who did not manage to become parents at all during the time period, and the researchers were not able to link the data to PSA values. Yvonne Lundberg Giwercman says their results are important for healthcare to be more thorough in following up the men who receive assisted reproduction. The researchers welcome further studies to explore the risk of prostate cancer in men treated for infertility. Studies on the advantages and effectiveness of PSA screening for this risk group in the same way as what is currently offered other high risk groups, e.g. when there is a genetic predisposition.

For register studies, the national quality registers are of great value, and a reliable source as they are extensive and have long-term follow-ups. Despite that the researchers in this study were not able to prove the causes of the link and did not have PSA data, Yvonne Lundberg Giwercman says that the results indicate that infertile men are a high risk group for prostate cancer and that PSA testing is as justified for this patient category as for any other high risk group.

"In the future, we would like to take a closer look at the risk for cancer over a longer period of time than was possible in this study, as ICSI has only existed as a method since the 1990s. It would also be interesting to investigate factors such as socio-economical aspects, health and lifestyle factors in men seeking assisted reproduction", says Yvonne Lundberg Giwercman.